This project involves a detailed study of the effect of neuroleptic drugs on the metabolism of dopamine in the striatum, tuberculum olfactorium and nucleus accumbens of the rat. To be included in the study are drugs which induce a high incidence of extra-pyramidal effects (e.g. haloperidol) and drugs which produce little or no extra-pyramidal effects (e.g. clozapine). Also to be studied are several butyrophenone and phenothiazine analogs with reported poor anti-psychotic efficacy. These studies include the generation of dose-response and time-action curves for acute drug treatment and a comparison of acute vs chronic drug treatment on dopamine metabolism. The dynamics of dopamine metabolism in the striatum and meso-limbic structures will be studied. Correlations of drug effects in the animal model with clinical data generated by Drs. S. Gershon and B. Angrist of the N.Y.U. Department of Psychiatry will be made. BIBLIOGRAPHIC REFERENCES: Wilk, S., Watson, E. and Glick, S.D. Dopamine metabolism in the tuberculum olfactorium. Europ. J. Pharmac. 1975, 30:117-120. Wilk, S., Watson, E. and Travis, B. Evaluation of dopamine metabolism in rat striatum by a gas chromatographic technique. Europ. J. Pharmac. 1975, 30:238-243.